post-TIPS Hepatic Encephalopathy (HE) MedDRA version: 21.1 Level: PT Classification code 10019660 Term: Hepatic encephalopathy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10076204 Term: Minimal hepatic encephalopathy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.1 Level: PT Classification code 10066599 Term: Hepatic encephalopathy prophylaxis System Organ Class: 10042613 - Surgical and medical procedur
Conditions
Sponsors
Academic Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Elective TIPS placement for refractory ascites or recurrent variceal bleeding: • Recurrent tense ascites and one or more of the following criteria: i. Not responding to the maximal dose of diuretics (400mg spironolactone and 160mg furosemide). ii. Kidney insufficiency (Creatinine > 135 umol/L) induced by diuretics. iii. Electrolyte disturbances (Sodium 5.5 mmol/l) induced by diuretics. iv. Not tolerating higher dose of diuretics (e.g. because of subjective side effects like muscle cramps). • (Recurrent) variceal bleeding, not responsive to treatment with endoscopic band ligation and/or beta-blockers, with a high risk of failure of endoscopic treatment: i. Patients with a variceal bleeding and Child-Pugh C (10-13 points) cirrhosis ii. Patients with a variceal bleeding, Child-Pugh B and an active bleeding during endoscopy 2. Age = 18 years 3. Confirmed liver cirrhosis as documented by liver biopsy, elastography (e.g. Fibroscan) or combination of usual radiological and biochemical criteria. 4. Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 226 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Any absolute contraindications for TIPS placement: a. History of hepatic encephalopathy grade II-IV without precipitating factor b. Heart failure NYHA = grade 3 c. Hepatocellular carcinoma (multifocal or large or centrally located) d. Systemic infection / sepsis e. Severe pulmonary hypertension f. Unrelieved bile duct obstruction g. Technically not feasible h. Poor liver function (MELD score > 20) 2. Use of ciclosporin 3. Life-threating variceal bleeding with emergency TIPS placement 4. Age > 80 years 5. Non-cirrhotic portal hypertension 6. Portal vein thrombosis 7. Current or recent (<3 months) use of rifaximin 8. Overt neurologic diseases such as Alzheimer’s disease, Parkinson’s disease 9. HIV 10. Pregnant or breastfeeding women 11. Patients refusing or unable to sign informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the prophylactic administration of lactulose and rifaximin in patients who undergo Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement, to lower the incidence of post-TIPS over hepatic encephalopathy (OHE) within the first three months. ;Secondary Objective: 1.ninety day mortality; 2.transplant-free survival; 3.the development of a second episode of OHE within the first three months after TIPS placement; 4.the development of OHE between three and twelve months after TIPS placement; 5.the change in PHES and S-ANT1 test during the study: at time-points week 4, week 12 and week 52, compared to baseline; 6.differences in molecular composition of peripheral / portal blood samples at TIPS placement; 7.differences in molecular composition of peripheral blood samples at baseline, compared to day 0, week 4, week 12, and week 52; 8.quality of life; 9.costs and cost-effectiveness.;Primary end point(s): Primary endpoint is the development of OHE within three months after TIPS placement determined by the West Haven criteria.;Timepoint(s) of evaluation of this end point: Three months after TIPS placement. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are 90 day mortality; development of a second episode of OHE within the first three months; development of OHE in the period between three and twelve months after TIPS placement; development of MHE between TIPS placement and twelve months after placement; time to development of OHE or MHE episodes; the increase of the PHES, S-ANT1 score and LFI compared to baseline. Difference in the composition of portal blood samples, drawn at TIPS placement. Difference in the composition of peripheral blood samples, drawn at different study timepoints. Furthermore, quality of life will be assessed by the Liver Disease Symptom Index 2.0 (LDSI 2.0) and EQ-5D-5L questionnaires. Costs will include costs of health care, productivity loss due to sick leave from work and out-of-pocket expenses.;Timepoint(s) of evaluation of this end point: Quality of life is measured at baseline, three and twelve months after TIPS placement. | — |
Countries
Belgium, Netherlands
Contacts
Public ContactLeverresearch
Academic Medical Centre
Outcome results
None listed